There has long been considerable interest in the noninvasive monitoring of body chemistry. There are 16 million Americans with diabetes, all of whom would benefit from a method for noninvasive measurement of blood glucose levels. Using currently accepted methods for measuring blood glucose levels, many diabetics must give blood five to seven times per day to adequately monitor their health status. With a noninvasive blood glucose measurement, closer control could be imposed and the continuing damage, impairment and costs caused by diabetes could be minimized.
Blood oximetry is an example of an application of electronic absorption spectroscopy to noninvasive monitoring of the equilibrium between oxygenated and deoxygenated blood (U.S. Pat. No. 5,615,673, issued Apr. 1, 1997). Similarly, vibrational spectroscopy is a reliable mode of quantitative and qualitative ex vivo analysis for complex mixtures, and there are reports of in vitro applications of this method to metabolically interesting analytes (S. Y. Wang et al, 1993, Analysis of metabolites in aqueous solution by using laser Raman spectroscopy, Applied Optics 32(6):925–929; A. J. Berger et al., 1996, Rapid, noninvasive concentration measurements of aqueous biological analytes by near infrared Raman spectroscopy, Applied Optics 35(1):209–212). Infrared measures, such as vibrational absorption spectroscopy, have been applied to skin tissue, but with success limited by unavailability of suitable light sources and detectors at crucial wavelengths, and by heating of the tissue due to the absorption of incident radiation (U.S. Pat. No. 5,551,422, see also R. R. Anderson and J. A. Parrish, 1981, The Optics of Human Skin, J. Investigative Dermatology 77(1):13–19). Previous attempts to provide methods for noninvasive blood glucose monitoring are summarized in U.S. Pat. No. 5,553,616, issued on Sep. 10, 1996.
Optimal application of noninvasive techniques for blood analysis will requite improved methods for isolating signals attributable to blood versus surrounding tissues. Tissue modulation is an effective means of differentiating between mobile and static phases for in vivo spectroscopic applications. When the interest is specifically in the most mobile fluid, i.e. blood, then tissue modulation is essential for the application of vibrational spectroscopy. Earlier methods of tissue modulation based on application of mechanical pressure in such a manner as to affect blood flow by changing the pressure field driving the blood in the vasculature simultaneously with physically deforming the vasculature. This has the disadvantage of inducing small variability in the spectroscopic signals, partly due to the induction of actual small variations in the spectroscopic properties of the vasculature as well as that of the blood.
There is a continuing need to improve upon the process of tissue modulation and the invention disclosed herein teaches how to apply the pressure more precisely and perform the necessary optical tasks so as to maximize the blood tissue modulation while minimizing the spectroscopic variation of the background static tissues.